Exercise training for management of peripheral arterial disease: a systematic review and meta-analysis.

BACKGROUND: Peripheral arterial disease (PAD), a chronic condition with debilitating clinical sequelae, leads to reduced walking activity and increased mortality risk.
OBJECTIVE: We sought to quantify expected benefits elicited via exercise training in people with PAD and aimed to clarify which prescriptions were optimal. DATA SOURCES: We conducted a systematic search (PubMed, CINAHL, Cochrane controlled trials registry; 1966-31 July 2013). STUDY SELECTION: We included randomized controlled trials (RCTs) of exercise training versus usual medical care in persons with PAD. Studies were assessed by two reviewers, 41 of 57 (72%) of RCTs met selection criteria. DATA EXTRACTION AND SYNTHESIS: Data extraction sheets were used to record data and two reviewers cross-checked data. Included study authors were asked for missing data. MAIN OUTCOMES AND MEASURES: Primary outcome: change in aerobic capacity (peak VO2). Secondary outcomes: ankle-brachial index (ABI), flow-mediated dilatation, 6-minute walk claudication distances (initial and absolute) and graded treadmill (initial and absolute) distances. The primary hypothesis was that peak VO2 would increase with exercise training. Using sub-analyses, we also aimed to clarify what types of exercise prescription would provide patients with most benefit; hypotheses were developed a priori.
RESULTS: Exercise training produced significant peak VO2 improvements with mean difference (MD) 0.62 ml·kg(-1)·min(-1) (95% CI 0.47-0.77; p < 0.00001); 6-minute walk initial claudication MD 52.7 m (95% CI 24.7-80.6 m; p = 0.0002); total walking distance MD 34.9 m (95% CI 25.6-44.1 m; p < 0.00001); graded treadmill initial claudication MD 68.8 m (95% CI 54.4-83.2 m; p < 0.00001); absolute claudication distance MD 41.0 m (95% CI 28.8-53.2 m; p < 0.00001)); but not ABI (p = 0.12) or flow mediated dilatation (FMD) (p = 0.96). Sub-analyses of change in peak VO2 after arm cranking showed a MD of 1.91 ml·kg(-1)·min(-1) (95% CI 1.28-2.54, p < 0.00001). Sub-analysis of peak VO2 according to exercise training pain thresholds suggested that no-to-mild pain may be superior (MD 0.79 ml·kg(-1)·min(-1) [95% CI 0.45-1.14, p < 0.00001]) to moderate-to-maximum training pain (MD 0.49 ml·kg(-1)·min(-1) [95% CI 0.31-0.66, p < 0.00001]). CONCLUSIONS AND RELEVANCE: Exercise training improves cardio-respiratory fitness, pain-free and total flat-ground walking distances, as well as graded treadmill performance in PAD. Exercise prescriptions for PAD may consider arm cranking as well as lower limb exercise, possibly at short vigorous intensity intervals, but only to a threshold of mild pain.